Background <p>A critical challenge in therapies for glioblastoma is systemic immunosuppression which is associated with poor response to therapies and thus correlated with worse outcomes. In this study we assess whether immune cytokines at baseline after diagnosis and during therapy are associated with outcome and may serve as an early biomarker predictive of treatment outcome.</p> Methods <p>Patients were enrolled in a prospective, single institution, immune surveillance study. Peripheral blood was collected prior to initiating treatments and weekly during concurrent radiation and chemotherapy. Cytokine levels were measured from plasma samples isolated from peripheral blood. The cytokines were categorized as proinflammatory or anti-inflammatory. Baseline levels and dynamic changes in the levels of cytokines were analyzed for association with survival.</p> Results <p>15 patients and 8 healthy controls were enrolled. At baseline, a majority immunosuppressive cytokines (IL-10, M-CSF, BTLA, PD-L1, LAG-3, PD-1, TIM-3, CTLA-4, TGFβ2 and TGFβ3) were elevated. The only proinflammatory cytokines associated with survival were IP-10, MCP-1, and IL-12p70 (according to the ANOVA analysis (<i>p</i> &lt; 0.05)). A dynamic increase in the levels of a select proinflammatory cytokines at end of radiation (IL-34, and IL-12 p70) was associated with poor survival as was increased MCP-1 in those with unmethylated glioblastoma. No association between outcomes and dynamic changes in remaining proinflammatory cytokines or any of the immunosuppressive cytokines was noted.</p> Conclusions <p>In this exploratory study, our data suggests that in patients with glioblastoma, measurements of plasma cytokines at diagnosis may predict outcomes. In addition, the dynamic changes in the cytokine levels could similarly serve as a biomarker guiding treatments. Future studies integrating clinical and patient specific immunological variables are required.</p>

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Radiation immunodynamics: association of baseline and longitudinal cytokine levels during radiotherapy in glioblastoma with survival

  • Sushant Puri,
  • Lindsey Sloan,
  • Michele Doucet,
  • Lisa Katulis,
  • Kristin Redmond,
  • Harry Quon,
  • Christopher Jackson,
  • Michael Lim,
  • Drew Pardoll,
  • Charles Eberhart,
  • Christopher Thoburn,
  • Sudipto Ganguly,
  • Peng Huang,
  • Lawrence R. Kleinberg

摘要

Background

A critical challenge in therapies for glioblastoma is systemic immunosuppression which is associated with poor response to therapies and thus correlated with worse outcomes. In this study we assess whether immune cytokines at baseline after diagnosis and during therapy are associated with outcome and may serve as an early biomarker predictive of treatment outcome.

Methods

Patients were enrolled in a prospective, single institution, immune surveillance study. Peripheral blood was collected prior to initiating treatments and weekly during concurrent radiation and chemotherapy. Cytokine levels were measured from plasma samples isolated from peripheral blood. The cytokines were categorized as proinflammatory or anti-inflammatory. Baseline levels and dynamic changes in the levels of cytokines were analyzed for association with survival.

Results

15 patients and 8 healthy controls were enrolled. At baseline, a majority immunosuppressive cytokines (IL-10, M-CSF, BTLA, PD-L1, LAG-3, PD-1, TIM-3, CTLA-4, TGFβ2 and TGFβ3) were elevated. The only proinflammatory cytokines associated with survival were IP-10, MCP-1, and IL-12p70 (according to the ANOVA analysis (p < 0.05)). A dynamic increase in the levels of a select proinflammatory cytokines at end of radiation (IL-34, and IL-12 p70) was associated with poor survival as was increased MCP-1 in those with unmethylated glioblastoma. No association between outcomes and dynamic changes in remaining proinflammatory cytokines or any of the immunosuppressive cytokines was noted.

Conclusions

In this exploratory study, our data suggests that in patients with glioblastoma, measurements of plasma cytokines at diagnosis may predict outcomes. In addition, the dynamic changes in the cytokine levels could similarly serve as a biomarker guiding treatments. Future studies integrating clinical and patient specific immunological variables are required.